Pemphigoid is a skin disease classified as a type of acquired bullous dermatosis among bullous dermatoses. It is an autoimmune disease classified into bullous pemphigoid (including nodular pemphigoid), cicatricial pemphigoid (benign mucosal pemphigoid), herpes gestationis, and juvenile pemphigoid. Cicatricial pemphigoid (benign mucosal pemphigoid) is further subclassified into anti-BP180 type cicatricial pemphigoid, anti-laminin 5 type cicatricial pemphigoid, and ocular cicatricial pemphigoid.
Of these diseases, bullous pemphigoid (BP) is one of representative autoimmune bullous dermatoses in the field of dermatology. Its characteristic clinical symptoms start with edematous erythemas. Then, tense blister, large and small, develop in erythematous plaques, and only blister appear occasionally. These symptoms occur mainly in the extremities and trunk with a high incidence, rupture and form erosions. Erosions, if systemically generated, may cause bacterial infection, and losses of water and protein in the body. Thus, edemas may develop systemically, or electrolyte abnormality in the blood and dehydration may occur, resulting in a worsened generalized condition. Pruritus is frequently noted as a subjective symptom. In terms of age, BP occurs most frequently in elderly people at 70 years of age or higher, but may rarely occur in children and young persons. Histopathological findings include subepidermal blisters, and inflammatory cell infiltrations predominantly of the eosinophilic origin. The direct immunofluorescence technique shows deposition of IgG and C3 in the basement membrane zone. Visceral malignant tumor may be occasionally involved as a complication, partly because BP occurs most frequently in the elderly.
In the treatment of pemphigoid typified by BP, external use of corticosteroids has so far been performed for erythema as a dermal symptom, and external use of EKSALB® or zinc oxide ointment (unguentum simplex) has been performed for erosion. Since external use of such drugs alone has proved insufficient in efficacy, however, oral administration of tetracycline antibiotics (MINOMYCIN®, ACHROMYCIIN®), nicotinamide, and corticosteroids has been implemented for systemic administration. If these treatments are still ineffective, systemic administration of immunosuppressants or plasmapheresis has been carried out. For pruritus, antihistaminics or antiallergic drugs have been administered as symptomatic therapies.
IFN-γ, on the other hand, has been demonstrated to have various biological actions, since it was discovered as a virus proliferation inhibiting factor produced by cells. Studies aimed at its clinical applications based on these actions have been conducted to show its effectiveness against atopic dermatitis, herpesvirus infection, and cutaneous T cell lymphoma among skin diseases. However, the results of investigation of the effectiveness of IFN-γ against pemphigoid have not been reported. Nor have there been any reports of cases of its use in the clinical setting.
In treating pemphigoid, it requires a follow-up care for a long term even after it is alleviated and nearly healed, because this disease is an autoimmune disease. Usually, its treatment begins with the oral administration of tetracycline antibiotics and nicotinamide whose systemic burden is light. However, the oral administration of these drugs alone is not sufficiently effective in many patients, and the systemic administration of corticosteroids is often concomitantly used. In the systemic administration of corticosteroids, large doses are administered at the start of treatment, and often produce an excellent effect. However, hospital stay for about 2 months is required until the dose is decreased to a safety dose permitting treatment at the outpatient clinic. If the corticosteroids prove ineffective, systemic administration of immunosuppressants or plasmapheresis may be used concomitantly.
In the elderly, such treatments performed for long periods are prone to cause complications, such as hypertension, diabetes, osteoporosis, interstitial pneumonia, and bacterial infection. Once such complications occur, therapy for their symptoms may be needed to lengthen the period of hospitalization to 3 to 4 months. Furthermore, the patients may be extremely debilitated, and die of complications. Alternatively, while the doses of the administered drugs are decreased, eruptions may be aggravated. Increasing the doses again may postpone discharge from the hospital, posing difficulty with treatment.
Hence, treatment with a pharmaceutical is desired, the pharmaceutical which, when used alone, is effective, is fast-acting and involves few side effects, whose action is persistent for a long term, and which enables a corticosteroid or an immunosuppressant, if used concomitantly, to be promptly decreased in dose, even if recurrence of pemphigoid is noted during treatment with the pharmaceutical. In the presence of such a pharmaceutical, the patient would be able to leave the hospital and return to society early. In the event of recurrence, rehospitalization for a short term would be able to achieve successful treatment. Against the background of these circumstances, the present invention has, as an object, the provision of a pharmaceutical which can solve the above-described problems in the therapy of pemphigoid.